Oral delivery of oily, water-insoluble nutraceutical compounds such as vitamin E is problematic due to the fact that such lipophiles are not well absorbed by the gastrointestinal tract. Oral supplementation of nutraceuticals is particularly problematic for patients having malabsorption conditions. Researchers have found that water-solubilized lipophilic compounds are more readily absorbed by the gastrointestinal tract.
A desirable oral dosage form for administering water-solubilized lipophiles is an aqueous oil-in-water emulsion, especially where patients have difficulty swallowing tablets and capsules. In such systems, the lipophile is solubilized and dispersed throughout the aqueous phase via a solubilizing agent. However, in order to maintain stability so that the lipophilic dispersed phase remains homogeneously distributed throughout the aqueous continuous phase of the emulsion, it is necessary to limit the amount of the solubilized active lipophile in the emulsion to a relatively low concentration. Thus, an undesirably large dosage size would be necessary to deliver an effective amount of nutraceutical lipophile. Moreover, this low “loading” limitation also limits the ability of formulations to include a complex blend of different lipophiles at a reasonable potency. For example, the low loading limitation has precluded a commercially acceptable formulation of an aqueous emulsion containing a blend of all eight homologs of natural source vitamin E because the dosage size would be larger than the acceptable amount of less than about 4 teaspoons (20 mL). Thus, it should be appreciated that it is imperative to use a very effective solubilizing agent in an oil-in-water emulsion. Formulators have found that Vitamin E TPGS is a particularly desirable solubilizing agent. Vitamin E TPGS is a water-soluble form of natural-source vitamin E prepared by esterifying d-alpha-tocopheryl acid succinate with polyethylene glycol 1000. Vitamin E TPGS is a well known compound having a chemical formula of C33O5H54(CH2CH2O)n, where “n” represents the number of polyethylene oxide moieties attached to the acid group of crystalline d-alpha tocopheryl acid succinate. Vitamin E TPGS is hereinafter referred to as simply “TPGS” for convenience.
The tocopherol portion of TPGS is nutraceutically active as a vitamin E source. Thus, the inclusion of TPGS in an aqueous formulation of a lipophile yields the dual functions of providing additional dietary vitamin E and providing solubilization of the lipophile.
While greater amounts of TPGS generally provide more solubilization of the lipophile, TPGS is a relatively expensive material. Yet another critical limiting factor controlling the maximum amount of TPGS in an aqueous emulsion is the fact that the administration of an excess amount of vitamin E, regardless of the source, can overdose a patient with vitamin E. Thus, the nutraceutical potency of an aqueous emulsion of lipophile is further limited by these additional limitations on the amount of TPGS as solubilizing agent.
In light of the above, it is an object of the present invention to provide an aqueous TPGS-solubilized emulsion of a lipophilic nutraceutical that overcomes the above limitations. It is a further object of the present invention to provide a stable aqueous emulsion delivering a higher potency of active nutraceutical lipophile. It is a still further object of the present invention to provide a higher potency aqueous emulsion having a solubilized blend of a higher number of different lipophiles at a higher concentration level than has previously been attainable, with an effective blend of the eight vitamin E homologs being a particularly desired object of this invention. Lastly, it is an object of the present invention that the aqueous emulsion provided be sufficiently concentrated so that an effective amount of lipophilic nutraceutical is delivered in a dosage size no greater than about 4 teaspoons (20 mL).